Structure-activity relationship studies of HIV-1 integrase oligonucleotide inhibitors

Julia Agapkina, Timofei Zatsepin, Ekaterina Knyazhanskaya, Jean Francois Mouscadet, Marina Gottikh

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)

Abstract

Integration of human immunodeficiency virus type 1 DNA into an infected cell genome is one of the key steps of the viral replication cycle. Therefore, viral enzyme integrase, which realizes the integration, represents an attractive and validated target for the development of new antiviral drugs. In this paper, the anti-integrase activity of a series of conjugates of single-stranded oligonucleotides with hydrophobic molecules was tested, and the structure-activity relationships were also analyzed. Both oligonucleotide and hydrophobic parts of the conjugates influenced the inhibitory potency. Conjugates of 11-mer phosphorothioate oligonucleotides with 6-carboxy-4,7, 2′,4′,5′,7′-hexachlorofluorescein (HEX) were found to be the most efficient inhibitors (IC 50 = 20 nM) and might be considered as lead compounds for further development of integrase inhibitors.

Original languageEnglish
Pages (from-to)532-537
Number of pages6
JournalACS Medicinal Chemistry Letters
Volume2
Issue number7
DOIs
Publication statusPublished - 14 Jul 2011
Externally publishedYes

Keywords

  • HIV-1 integrase
  • inhibitor
  • oligonucleotide conjugate
  • xanthene

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